This proposal requests funds for the purchase of a state of the art small animal radiation research platform (SARRP) irradiator. SARRP is first of its kind that is commercially available and that combines cone beam computed tomography (CT) imaging with micro-irradiation enabling basic scientists and translational researchers to utilize the conformal, fractionated radiotherapy protocols that are currently used in the clinic in studies with small animals. This is essential for translating laboratory studies that combine radiotherapy with chemo- or immunotherapies. Studies on the normal tissue effects of radiation also require highly conformal radiation treatments. The goal in many cases is to limit radiation exposure to one organ (e.g. the heart) or part of an organ (e.g. one lung or one kidney) to facilitate analysis of normal tissue damage without confounding effects of other normal tissue damage or using unrealistically high single radiation doses. Presently at Virginia Commonwealth University there is a Cs137 irradiator, a retired clinical Co60 unit and the clinical linear accelerators (linasc). The Co60 unit is being decommissioned because of cost and security issues. The Cs137 irradiator does not provide conformal dose distributions. The linacs in their clinical configurations do not have the conformal properties of the SARRP that are optimal for small animal studies. In addition, they can be only operated after clinic hours and there are always the concerns of patient safety (e.g allergies). The SARRP will be installed in the Massey Cancer Center vivarium minimizing transport of valuable transgenic mice outside the "clean" vivarium. The major users are NIH funded and come from the Departments of Radiation Oncology, Human Genetics, Biochemistry, Neurosurgery and Pharmacology/Toxicology. Their studies range from studies with breast, prostate and colon cancers to studies of normal tissue responses including colon, lung, and heart and combine radiotherapy with either chemotherapeutics or immunotherapy. One investigator has on-going studies on PET (Positron Emission Tomography) using a PET/CT scanner designed for small animal studies in the Molecular Imaging Facility at Virginia Commonwealth University. With appropriate image registration which the SARRP can accommodate, PET imaging for hypoxia or tumor cell proliferation with probes synthesized in the cyclotron at Virginia Commonwealth University can be used to develop biologically guided radiotherapy protocols using SARRP. For all investigations the ability to deliver precise conformal radiation to either tumor or normal tissue is essential for testing mechanistic hypotheses in vivo and their translation into testable treatment protocols.